Screening system and method for analyzing a plurality of biosensors

ABSTRACT

A screening device and a method are described herein which can automatically handle and measure (interrogate) a plurality of sensor carriers (i.e., multiwell plates, microplates) with multi-dimensionally arranged, temperature-compensated or temperature-compensatable optical sensors, while maintaining a substantially constant temperature gradient for a relatively long period of time around the optical sensors where temperature compensation has been performed on the sensor carriers.

BACKGROUND OF THE INVENTION

1. Field of the Invention

The present invention relates to a screening system and method forautomatically carrying out biochemical, cell biological or molecularbiological analyses of liquids at the surfaces of a multiplicity ofoptical sensors/biosensors which are located in standardized multiwellplates (or other types of multi-vessel systems such as bars, strips,slides, rotor cuvettes etc. . . . ).

2. Description of Related Art

Today there is considerable interest in developing a screening systemwhich can automatically carry out biochemical, cell biological ormolecular biological analyses of liquids at the surfaces of amultiplicity of optical sensors/biosensors (or at least on parts of thesurfaces of those optical sensors/biosensors) located in standardizedmultiwell plates (or other multi-vessel systems such as bars, strips,slides, rotor cuvettes etc. . . . ). The targeted analyses often includedrug discovery, drug screening, laboratory diagnosis and fundamentalresearch. In these high sensitivity analyses, it is critical thatfactors which could lead to spurious changes in the measured output(optical response) of the optical sensor/biosensor be carefullycontrolled or referenced out. The factors which could lead to thesespurious changes include, for example, temperature changes, solventeffects, bulk index of refraction changes, and nonspecific binding. Thefactor which is of interest in this particular discussion is thechanging of the temperature.

The use of a standardized multiwell plate in these types of analyses isadvantageous because it allows known automated high throughput screening(HTS) systems and known manual fluid handling systems to be used inconjunction with the “special” optical sensors. The most desirablestandardized formats are the 96 multiwell plate (9 mm specimen spacing),the 384 multiwell plate (4.5 mm specimen spacing), and the 1536multiwell plate (2.25 mm specimen spacing). All of these multiwellplates cover the same rectangular area of roughly 130 mm×85 mm. However,the use of the standardized multiwell plate (or any of the otheraforementioned multi-vessel systems) can be problematic since it can bedifficult to control their temperature profile because their inner wellsare not able to adapt as quickly as their outer wells when there is achange in the ambient temperature.

Plus, if the multiwell plate is filled for example with water, then thewell contents are going to evaporate at different rates which also makesit difficult to control the temperature profile of the multiwell plate.For example, if the multiwell plate is placed in calm ambient air in anopen condition (without a cover), the peripheral regions will evaporatemuch more quickly than the middle regions, because the air above thewells on the edges is not saturated with water vapor as quickly as theair above the middle wells. As a consequence, these outer wells cool offmore quickly due to what is known in this field as evaporation cold.This effect is also present, although quantitatively reduced, if themultiwell plate is provided with a cover.

The liquid handling devices and storages facilities can also adverselyaffect the temperature profile of the multiwell plate. In particular,when the liquid handling device (pipetting device) is used to transferliquid onto a target multiwell plate it first takes up liquid from asource vessel (which is open for at least a short time) and thendispenses this liquid onto the target multiwell plate. As a result, theliquid handling device partially transfers to the target plate thetemperature profile of the source plate. If the source plate isre-filled by pumps from a supply (bottle, tank, etc.), then considerabletemperature profiles may be expected, especially if the source plate isfilled through one single inlet opening.

In the past, it has been assumed that the use of incubators to heat themultiwell plates would solve these temperature related problems.Probably, the most widely used automatic incubators are made byKendro/Liconic and Tomtec which are described in U.S. Pat. Nos.6,129,428 and 6,478,524 (the contents of which are incorporated byreference herein). In these incubators, the multiwell plates are storedin stacked arrangements such that they are freely accessible from belowand can thus be transported into-and-out of the incubators by ashovel-like handler. In addition, the stacked arrangements can bearranged on a support plate which continuously rotates to ensure abetter (more homogeneous) temperature of the multiwell plates. Moreover,these incubators can incorporate a blower which is used to provide a notvery well-defined intermixing of the air by which the multiwell platescan be further temperature-controlled. Unfortunately, in suchincubators, temperature gradients of several degrees is still detectableacross the diagonal of a multiwell plate. Also, in these incubatorswhere the temperature control is performed by the air (more generallygas) there is a very slow temperature adjustment with the multiwellplates.

It is known from the literature that this should be able to be donebetter. For instance, by using a temperature balancing body thatcontacts the full surface of the bottom of the multiwell plate thetemperature of the multiwell plate can be adjusted in a manner that isfaster and more homogeneous (see, DE 3441179 C2 and U.S. Pat. No.5,459,300 the contents of which are incorporated by reference herein).However, the literature does not describe how the multiwell platesthroughput per time unit in a screening system and the temperaturebalance of those multiwell plates can be suitably realized especiallywhen a screening system is going to be operating at it's sensitivitylimit. This problem and other problems are solved by the screeningdevice and method of the present invention.

BRIEF DESCRIPTION OF THE INVENTION

The present invention includes a screening device and a method which canautomatically handle and measure (interrogate) a plurality of sensorcarriers (i.e., multiwell plates, microplates) with multi-dimensionallyarranged, temperature-compensated or temperature-compensatable opticalsensors, while maintaining a substantially constant temperature gradientfor a relatively long period of time around the areas where temperaturecompensation has been performed on the sensor carriers.

BRIEF DESCRIPTION OF THE DRAWINGS

A more complete understanding of the present invention may be obtainedby reference to the following detailed description when taken inconjunction with the accompanying drawings wherein:

FIGS. 1A-1F are various diagrams illustrating different views of ascreening system in accordance with the present invention;

FIG. 2 is a diagram illustrating an exemplary measurement device whichcan be used within the screening system in accordance with the presentinvention;

FIG. 3 is a diagram illustrating an exemplary x-y moveable table whichcan be used within the screening system in accordance with the presentinvention;

FIGS. 4A-4C are three diagrams illustrating an exemplary equilibrationsystem (with a plurality of temperature compensation bodies) which canbe used within the screening system in accordance with the presentinvention;

FIGS. 5A-5B are two diagrams which are used to help explain how thescreening system can operate in a HTS (parallel) mode in accordance withthe present invention;

FIGS. 5C-5D are two diagrams which are used to help explain how thescreening system can operate in a batch (serial) mode in accordance withthe present invention;

FIGS. 6A-6D are various diagrams illustrating an exemplary sensorcarrier (microplate) which could be interrogated by the screening systemin accordance with the present invention;

FIGS. 7A-7B are diagrams illustrating two different types of sensorcarriers (slides) which could be interrogated by the screening system inaccordance with the present invention;

FIGS. 8A-8B are diagrams illustrating two different types of sensorcarriers (cuvette systems) which could be interrogated by the screeningsystem in accordance with the present invention;

FIGS. 9A-9C are diagrams illustrating the temperature distributionassociated with two exemplary microplates which are used to helpindicate an advantage of using the screening system in accordance withthe present invention;

FIG. 10 is a diagram which is used to help explain how the screeningsystem can compensate for temperature changes by interrogating bothsample wells and reference wells within a microplate in accordance withthe present invention;

FIGS. 11A-11B are diagrams which are used to help explain how thescreening system can compensate for temperature changes by interrogatingboth sample regions and buffer regions within single wells of amicroplate in accordance with the present invention;

FIG. 12 is a block diagram illustrating an exemplary temperaturecompensation body (located in the equilibration system of FIGS. 4A-4C)that can be used to help equalize the temperature of a microplate whichincorporates RIFS transducers in accordance with the present invention;

FIG. 13 is a block diagram illustrating an exemplary temperaturecompensation body (located in the equilibration system of FIGS. 4A-4C)that can be used to help equalize the temperature of a microplate whichincorporates RWG biosensors in accordance with the present invention;

FIG. 14 is a block diagram illustrating an exemplary temperaturecompensation body (located in the equilibration system of FIGS. 4A-4C)that can be used to help equalize the temperature of a microplate whichincorporates SPR biosensors in accordance with the present invention;

FIG. 15 is a block diagram illustrating an exemplary temperaturecompensation body (located in the equilibration system of FIGS. 4A-4C)that can be used to help equalize the temperature of a microplate whichincorporates waveguide interferometers in accordance with the presentinvention;

FIG. 16 is a diagram illustrating an exemplary measurement system thatcan be used by the screening system to interrogate RWG biosensors inaccordance with the present invention;

FIGS. 17A-17D are graphs which illustrate the temperature developmentover time within an exemplary microplate without using a temperaturecompensation body (see 0 minute) and with using a temperaturecompensation body (see time after 0 minutes) that helps indicate anadvantage of using the screening system in accordance with the presentinvention;

FIG. 18 is a diagram illustrating an exemplary measurement system thatcan be used by the screening system to interrogate waveguideinterferometers in accordance with the present invention; and

FIG. 19 is a diagram illustrating an exemplary measurement system thatcan be used by the screening system to interrogate RIFStransducers/sensors in accordance with the present invention.

DETAILED DESCRIPTION OF THE DRAWINGS

Referring to FIGS. 1-19, there are various diagrams which illustrate ascreening system 100 and the various components incorporated therein inaccordance with the present invention. As shown in FIGS. 1A-1F, thescreening system 100 includes a control unit 102 and atemperature-controlled measurement chamber 104 which contains anequilibration system 106, a measurement system 108 and a handling system112. Basically, the screening system 100 is designed to automaticallyhandle and measure (interrogate) a plurality of sensor carriers 110(i.e., multiwell plates 110, microplates 110) with multi-dimensionallyarranged, temperature-compensated or temperature-compensatable opticalsensors, while maintaining a substantially constant temperature gradientfor a relatively long period of time around the areas where temperaturecompensation has occurred on the sensor carriers 110 (an exemplarymicroplate 110 is shown in FIGS. 6A-6B).

The screening system 100 is able to perform this measurement(interrogation) by using the equilibration system 106, the measurementsystem 108 and the special handling system 112. Plus, it may bebeneficial if the screening system 100 also included an insidetemperature sensor 114 (which measures the temperature of the air/gaswithin the measurement chamber 104) and an outside temperature sensor116 (which measures the outside temperature in the vicinity of thescreening device 100). Then, the screening systems 100 and in particularthe control unit 102 could use the readings from the two sensors 114 and116 to check whether the measurement chamber 104 is operating in thedesired ambient temperature range, which may be important to know so asto meet the necessary prerequisites for a temperature control algorithm.

As shown, the screening device 100 also has a take in/out mechanism 118(which is mounted to a motor-displaceable frame) for taking a sensorcarrier 110 in-and-out of the measurement chamber 104. The take in/outmechanism 118 can cooperate with an outside door of the measurementchamber 104 like a spring forced flap and internally seal the openingagainst a lock shaft by a simple shield, when the outside door is open.This simple lock principle keeps the exchange of air between themeasurement chamber 104 and the outside environment to a minimum duringthe replacement of a sensor carrier 110.

The measurement of the sensor carriers 110 is enabled by positioning oneof the sensor carriers 110 relative to a measurement channel ormeasurement channels associated with a measurement device 120 (part ofthe measurement system 108) by using a motor-driven x-y moveable table122 (see FIGS. 2 and 3 for detailed illustrations of an exemplarymeasurement device 120 and an exemplary x-y moveable table 122) (note: astationary table may also be utilized). For this purpose, the x-ymoveable table 122 has a measurement nest 302 into which a sensorcarrier 110 is inserted and then moved so it is positioned in a correctspot over the measurement device 120. In this way, the sensors withinthe sensor carrier 110 can be sensed or scanned in a definable sequence.For a detailed discussion about some of the different types ofmeasurement devices 120 (and sensor carriers 110) that can be used inthis particular application, reference is made to the followingdocuments:

-   -   U.S. patent application Ser. No. 11/489,173 entitled “Label-Free        High Throughput Biomolecular Screening System and Method”.    -   U.S. patent application Ser. No. 11/027,547 entitled “Spatially        Scanned Optical Reader System and Method for Using Same”.    -   U.S. patent application Ser. No. 10/977,520 entitled        “Single-Fiber Launch/Receive System for Biosensing        Applications”.    -   U.S. patent application Ser. No. 10/856,572 entitled “Optical        Interrogation Systems With Reduced Parasitic Reflections and a        Method for Filtering Parasitic Reflections”.    -   U.S. patent application Ser. No. 11/058,155 entitled “Single        Mode (SM) Fiber Optical Reader System and Method for        Interrogating Resonant Waveguide-Grating Sensor(s)”.    -   U.S. patent application Ser. No. 10/602,304 entitled “Optical        Interrogation System and Method for Using Same”.    -   U.S. patent application Ser. No. 11/019,439 entitled “Arrayed        Sensor Measurement System and Method”    -   U.S. Pat. No. 6,785,433 entitled “Waveguide Grid Array and        Optical Measurement Arrangement”.    -   U.S. patent application Ser. No. 11/100,199 entitled “Optical        Interrogation System and Method for 2-D Sensor Arrays”.    -   U.S. Pat. No. 5,738,825 entitled “Optical Biosensor Matrix.    -   U.S. Pat. No. 7,629,173 entitled “Optical Reader System and        Method for Monitoring and Correcting Lateral and Angular        Misalignments of Label Independent Biosensors”.

The contents of these documents are incorporated by reference herein.

In the measurement chamber 104, there is the special transporting unit112 (internal plate handling system 112 with a gripper 113) whichaccepts a sensor carrier 110 from the take in/out mechanism 118 and thendeposits the sensor carrier 110 onto a temperature compensation body 128which is on an equilibration site 126 in the equilibration system 106(see FIGS. 4A-4C for detailed illustrations of an exemplaryequilibration system 106 and an exemplary temperature compensation body128). After a suitably selected equilibration time, the transportingunit 112 takes the sensor carrier 110 from the temperature compensationbody 128 and places it on the x-y moveable table 122 which is moved sothe measurement device 120 can interrogate the sensors within the sensorcarrier 110. Upon completion of the measurement, the transporting device112 transfers the sensor carrier 110 to the take in/out mechanism 118 orit takes a detour via the equilibration system 106 from which the sensorcarrier 110 is then transferred to the take in/out mechanism 118 anddischarged from the screening device 100.

The transporting device 112 can be an automatic manipulator (robotand/or gripper), which receives and transports the sensor carrier 110 ina force- or form-locking manner. The equilibration system 106 has aplurality of temperature compensation bodies 128 which are specificallydesigned to hold the sensor carriers 110 (see FIGS. 4A-4C and 12-13).Preferably, the specially designed temperature compensation bodies 128are of such construction that they represent a negative image of thesensor carrier's contour at least in its foot print and, thus, ifpossible, has full surface contact or at least a maximum possiblecontact, in terms of the surface, with the sensor carriers 110 (see FIG.4C which shows a temperature compensation body 128 for a 384-well RWGsensor carrier 110). Moreover, the specially designed temperaturecompensation bodies 128 have a sufficiently great heat capacity (thermalconductance) such that when the sensor carriers 110 are, placed on themthen those bodies 128 will not experience a substantial change intemperature. This can be satisfied if it is assumed that an initialtemperature of the sensor carriers 110 does not differ too much from adefined temperature (i.e., approximately 3 to 5° C.) within themeasurement chamber 104.

Moreover, the specially designed temperature compensation bodies 128could have a relatively low surface resistance with the sensor carriers110 such that any difference in heat can be quickly compensated. Asuitable surface resistance should be achieved if there is a maximumidentity and a low depth of roughness between the surfaces of thetemperature compensation bodies 128 and the sensor carriers 110. Thesurface resistance could also be reduced by pressing or sucking thesensor carriers 110 against the temperature compensation bodies 128.Furthermore, the surface resistance could be reduced by increasing themass of the sensor carriers 110. For instance, the mass of the sensorcarriers 110 themselves can be increased by placing covers/foils or aspecial heavy lid on top of them (the covers/foils also helps preventthe evaporation of the liquids from the sensor carriers 110). Ifdesired, the covers can be constructed specifically to be adapted to theparticular geometry of the sensor carriers 110. Or, the covers can beproduced such that they are disposable. Alternatively, the covers canhave a thin metal plate mounted/placed thereon to add the desiredadditional mass to the sensor carriers 110. Of course, it is importantthat the above-mentioned handling system 112, e.g. the gripper 113, cantransport these covers.

The storage of the sensor carriers 110 can be effected within theequilibration system 106 according to a simple FIFO (first in first out)scheme. This could be accomplished in several ways, for example, theequilibration system 106 could allow random access to the equilibrationsites 126 and then use the control unit 102 to implement the FIFOscheme. Or, the equilibration system 106 itself can be constructed as amechanical FIFO storage system. In contrast, it is also possible to havean equilibration system 106 that utilizes a LIFO (last in first out)storage scheme by following a restacking algorithm which would beimplemented by the control unit 102. Of course, the LIFO scheme could bedifficult to successfully perform because it requires the plate carousel130 to constantly move within the equilibration system 106.

The storage capacity, i.e. the number of equilibration sites at whichthe sensor carriers 110 can contact the temperature compensation bodies128, depends on the equilibrating time which is required to achieve asufficiently good, homogeneous heat distribution on the sensor carriers110. An important factor to consider in this connection is how great atemperature difference between the sample site and the reference site isallowed and how great the distance is between these two sites. If, forexample, a 384-well microplate 110 is used, and only every other well isfilled with compounds to examine binding, then referencing can beeffected in each case with the next well that is filled only with abuffer, the distance between both sites is thus 4.5 mm. Such a greatdistance would typically require that the 384-well microplate 110 spenda correspondingly prolonged equilibration time on the temperaturecompensation body 128.

In contrast, if referencing is effected within the well, then thedistance between sites can be reduced to approximately 1 mm, thusreducing the required, equilibration time that the 384-well microplate110 needs to spend on the temperature compensation body 128. The lastscenario would result in fewer temperature compensation bodies 128 beingneeded in the equilibration system 106. Lastly, it should be appreciatedthat the storage capacity is also related to the desired quality ofmeasurement (coefficient of variation), the resolution of the method ofmeasurement (molecule size ratio of the binding partners) and theaccepted average temperature of the incoming sensor carriers 110.

Preferably, the measurement device 120 (and x-y moveable table 122) islocated at a minimum possible distance from the equilibration system 106and the handling system 112. Both the measurement device 120 and thehandling system 112 should be constructed such that they each have ashort and spot contact with the sensor carrier 110. This helps prevent achange in the temperature distribution, set by the equilibration system106, from being made on the sensor carrier 110. Moreover, it should beensured that the handling system 112 transports the sensor carrier 110sufficiently quickly so as to prevent any noticeable change in thetemperature profile of the sensor carrier 110. Any interruption of thistransport and the subsequent measurement of the sensor carrier 100should not be permitted by the control unit 102.

If desired, the screening system 100 can include one or more temperaturesensors 118 a which are positioned near the opening of the take in/outmechanism 118. The temperature sensor(s) allow the control unit 102 todetermine the temperature of an incoming sensor carrier 110 in anon-contacting manner and to check whether the intended storage time ofthat sensor carrier 110 is sufficient for temperature equilibrationpurposes. Alternatively, the control unit 102 can use this type oftemperature reading to calculate the time that the incoming sensorcarrier 110 needs to be placed on the temperature compensation body 128to obtain the desired temperature profile on the sensor carrier 110. Ofcourse, a wide variety of temperature sensor(s) can be used to performthis measurement such as infrared sensors, electronic contactthermometers, or a combination of color sensors andtemperature-sensitive dyes (e.g. liquid crystals or fluorescentlanthanoid-ligand complexes) which are placed on the incoming sensorcarrier 110. Plus, it is to be expected that radio-frequency basedtransponders are going to replace the identification barcode labelswhich are commonly used today to identify sensor carriers 110(microplates 110). As an additional function, these electronicradio-frequency based transponders could transmit the currenttemperature of the sensor carrier 110, if their semi-conductor structurealso has a temperature-sensitive range of operation.

These temperature sensor(s) may also provide important information inconnection with an optional calculation of the dew point. For thispurpose, the temperature of the incoming sensor carrier 110, thetemperature inside the measurement chamber 104 and the air humidityinside the measurement chamber 104 are used to calculate whether thereis a risk of water condensing on the sensor carrier 110. There would bea risk of water condensing on the sensor carrier 110 if the sensorcarrier 110 is colder than the air inside the measurement chamber 104.Since, part of the sensor carrier 110 is going to be in directmechanical contact with a temperature compensation body 128, thiscondensate could possibly affect the temperature equilibration. Plus,this condensation could also interfere with the optical sensor lightpath used by the measurement device 120 to interrogate the sensors inthe sensor carrier 110. Excessive pollution of the temperaturecompensation bodies 128 would be a further undesired consequence ofwater condensation in the long run. The information concerning the airhumidity may be obtained by using an electronic sensor (e.g., SENSIRION,Switzerland) which would be placed in the measurement chamber 104. Or,the air humidity may be obtained by using an external source ofinformation, e.g. a LIMS (Laboratory Information Management System).

If the control unit 102 determines that the incoming sensor carrier 110has an admissible temperature, then the sensor carrier 110 istransported to and deposited onto one of the temperature compensationbodies 128. In contrast, if the incoming sensor carrier 110 does nothave an admissible temperature, then the control unit 102 makes acase-based differentiation. For instance, if the sensor carrier 110 hasan inadmissible temperature and there is little risk of watercondensing, then the control unit 102 can instruct that the sensorcarrier 110 be transported to and deposited onto one of the temperaturecompensation bodies 128. However, the control unit 102 should at leastmake an entry into a data file associated with this particular sensorcarrier 110 which indicates that the incoming temperature wasinadmissible. Or, the control unit 102 can simply reject the sensorcarrier 110 if it does not have an admissible temperature.

The implementation of this particular procedure can have far-reachingand important consequences. For instance, this procedure can placeconsiderable work on the control unit 102 and in particular on theautomatization software, work flow manager and/or scheduler. Thus, it isdesirable if the sensor carriers 110 are temporarily stored in anexternal plate storage system, i.e. incubated in advance at roomtemperature, for a predetermined amount of time before they are placedwithin the screening system 100. This is not necessarily a disadvantagesince the binding of molecules to the surface of the sensors oftenrequires a certain amount of incubation time and thus, during automaticoperation, this pre-incubation already needs to be performed. If thescreening system 100 is controlled by suitable software (for example, ascheduler), then these incubation times would have little effect (duringthe start-up phase of a screen) on the throughput of the sensor carriers110. Such external incubators or storage units are often referred to asmicroplate hotels and are manufactured by, for example, Liconic orKendro/Thermo.

A description is provided next about three exemplary ways the screeningsystem 100 could be used to perform measurement assays (e.g., standalone assays, scheduler controlled assays). To help describe some of thedifferent ways that the screening system 100 could be used it is usefulto recall that the screening system 100 includes the followingcomponents: the take in/out mechanism 118 (plate carriage 118), thehandling system 112 (plate gripper 113), the equilibration system 106(including a rotating plate carousel 130 with multiple levels andquadrants of temperature compensation bodies 128), the measurementsystem 120 (including the measuring module 108) (see FIGS. 1A-1F). Plus,the screening system 100 has an entry/exit door (flap) that is closed bya spring force when the take in/out mechanism 118 is not in an outsideposition. The preferred plate handler 112 can be a vertical mobilesystem which can reach all levels of the plate carousel 130 (inparticular it can reach between the individual temperature compensationbodies 128 on anyone carousel level), the take in/out mechanism 118 andthe measurement nest 302 on the x-y moveable table 122. In this example,the plate carousel 130 has several levels (shown five levels) each ofwhich are divided up into four quadrants on which there are secured thespecially designed temperature compensation bodies 128 (see FIGS. 4A-4Cand 12-13).

In the first example, the screening system 100 can be used to perform astand alone measurement assay by:

1. Putting a sensor carrier 110 onto the take in/out mechanism 118 (viahand or robot).

2. Moving the take in/out mechanism 118 into the measurement chamber 104via a door and positioning the sensor carrier 110 below a gripper 113 onthe handling system 112.

3. Grabbing the sensor carrier 110 using the gripper 113 on the handlingsystem 112.

4. Placing the sensor carrier 110 into the measurement nest 302 of thex-y moveable table 122 located above the measurement system 108.

5. Interrogating the sensor carrier 110.

6. Taking the sensor carrier 110 from the x-y moveable table 122 andmoving it to the take in/out mechanism 118.

7. Moving the sensor carrier 110 out of the measurement chamber 104 viathe door.

In the second example, the screening system 100 can be used to perform ascheduled controlled measurement assay by:

1. Putting a sensor carrier 110 onto the take in/out mechanism 118 (viahand or robot).

2. Moving the take in/out mechanism 118 into the measurement chamber 104via a door and positioning the sensor carrier 110 below a gripper 113 onthe handling system 112.

3. Grabbing the sensor carrier 110 using the gripper 113 on the handlingsystem 112.

4. Moving the sensor carrier 110 to a desired level between twoquadrants on the plate carousel 130.

5. Turning the plate carousel 130 to the target position.

6. Placing the sensor carrier 110 onto the desired temperaturecompensation body 128 located on the plate carousel 130 (start thetemperature equilibration).

7. Moving the temperature equilibrated sensor carrier 110 from the platecarousel 130 with the gripper 113 on the handling system 112 (if desiredone can move another temperature equilibrated sensor carrier 110).

8. Placing the sensor carrier 110 into the measurement nest 302 of thex-y moveable table 122 which is located above the measurement system108.

9. Interrogating the sensor carrier 110.

10. Taking the sensor carrier 110 from the x-y moveable table 122 andmoving it to the take in/out mechanism 118.

11. Moving the sensor carrier 110 out of the measurement chamber 104 viathe door.

In the third example, the screening system 100 can be used to perform ascheduled controlled measurement assay by:

1. Putting a sensor carrier 110 onto the take in/out mechanism 118 (viahand or robot).

2. Moving the take in/out mechanism 118 into the measurement chamber 104via a door and positioning the sensor carrier 110 below a gripper 113 onthe handling system 112.

3. Grabbing the sensor carrier 110 using the gripper 113 on the handlingsystem 112.

4. Moving the sensor carrier 110 to a desired level between twoquadrants on the plate carousel 130.

5. Turning the plate carousel 130 to the target position.

6. Placing the sensor carrier 110 onto the desired temperaturecompensation body 128 located on the plate carousel 130 (start thetemperature equilibration).

7. Moving the temperature equilibrated sensor carrier 110 from the platecarousel 130 with the gripper 113 on the handling system 112 (if desiredone can move another temperature equilibrated sensor carrier 110).

8. Placing the sensor carrier 110 into the measurement nest 302 of thex-y moveable table 122 which is located above the measurement system108.

9. Interrogating the sensor carrier 110.

10. Taking the sensor carrier 110 from the x-y moveable table and movingit to a free temperature compensation body 128 on the plate carousel 130only for parking/holding to have more freedom for the schedulingsoftware.

11. Taking the sensor carrier 110 from the plate carousel 130 and movingit to the take in/out mechanism 118.

12. Moving the sensor carrier 110 out of the measurement chamber 104 viathe door.

Of course, these three exemplary ways are not the only ways one canperform a measurement assay using the screening system 100. Forinstance, the screening system 100 can be operated in a HTS (parallel)mode in which a large number of sensor carriers 110 are placed in themeasurement chamber 104 and one-by-one the sensor carriers 110 areinterrogated by the measurement system 108. FIGS. 5A-5B illustrate anexemplary software design which could be used when the screening system100 is operating in the HTS (parallel) mode. Alternatively, thescreening system 100 can be operated in a batch (serial) mode in which alarge number of sensor carriers 110 are placed in the measurementchamber 104 and one-by-one the sensor carriers interrogated by themeasurement system 108. FIGS. 5C-5D illustrates an exemplary softwaredesign which could be used when the screening system 100 is operating inthe batch (serial) mode.

A description is provided next about different aspects and possiblealternatives associated with the screening system 100 that can be usedor implemented when performing a measurement assay in accordance withthe present invention. The topics discussed below are as follows:

-   1. Sensor carrier as microplate.-   2. Sensor carrier as slide.-   3. Sensor carrier as cuvette rotor with flow through cuvette sensor.-   4. Temperature distribution in microplates.

4.1 Temperature compensation interrogation scheme with adjacent well.

4.2 Temperature compensation interrogation scheme within a well.

-   5. Temperature compensation body for RIFS transducer/sensor.-   6. Temperature compensation body for grating coupler.-   7. Temperature compensation body for SPR sensor.-   8. Temperature compensation body for waveguide interferometer.-   9. Automatic measurement chamber.-   10. Measuring device for grating sensors.-   11. Equilibration operation in a microplate.-   12. Measuring device for waveguide interferometers.-   13. Measuring device for RIFS transducers/sensors.    1. Sensor Carrier 110 as a Microplate:

A typical microplate 600 arrangement according to the SBS standard(Journal of Biomolecular Screening, Vol 1, Number 4, 1996, pp. 163-168)consists of a frame 602, including a well structure 604 (holey plate604) that can be made of a plastic material, in most cases polystyrene,polypropylene or Cyclic Olefin Co-Polymer (f.e. Topas™), and of a bottom606 that can be made of glass (see FIGS. 6A and 6B for drawings of anexemplary 96-well microplate 600). The well structure 604 can beattached to the bottom 606 via adhesives 608, injection molding,ultrasonic bonding, laser or infrared welding etc. . . . .

In preparation for binding experiments, the target molecules can beplaced at the bottoms of the wells 610 in the microplate 600 by using aconventional liquid handling system (not shown). A biosensor 612 isshown located at the bottom of each well 610. In one embodiment, FIG. 6Cshows a side-view of a resonant waveguide grating (RWG) biosensor 612(which has an optical grating structure 614) that is located in a well610 as discussed in U.S. Pat. No. 4,815,843 (the contents of which areincorporated by reference herein). Alternatively, FIG. 6D shows aside-view of another type of biosensor 612 known as a ReflectometricInterference Spectroscopy (RIFS) sensor 612 that is discussed in U.S.Pat. No. 6,018,388 (the contents of which are incorporated by referenceherein).

2. Sensor Carrier 110 as a Slide:

Another important format which has been used in laboratories forconsiderably more years than microplates is the microscope specimencarrier, commonly referred to as a slide (see FIGS. 7A-7B whichillustrate an exemplary slide 700). The typical slide 700 has a size of25×75 mm² and is made from a planar glass plate or plastic plate. Thebasic dimensions of such slides 700 have been standardized by microscopemanufacturers. The slide 700 shown also has wells 702 fitted thereon orattached thereto. These wells 702 are rubber-sealed against or connectedto the planar plate by the methods already mentioned above with regardto the microplate 600. Wells 702 made of silicone rubber which areattached to glass are also known, and so are wall-free, planar glassstructures with alternating hydrophobic (better: ultraphobic) andhydrophilic (better: ultraphilic) regions. On these slides 700, theoptical structures/biosensors 612 already mentioned above can bemounted/formed.

Alternatively, these slides 700 can have formed thereon micro-opticalinterferometers 706 in which light can be coupled in-and-out via planargrating couplers (see FIG. 7B for a side view of an exemplarymicro-optical interferometer 706 which could be used in microplate 600).If such structures (wells 702 with biosensors 704 or micro-opticalinterferometers 706) are realized within a 9 mm grid, then these slides700 would be compatible with the double 8-well strips of conventionalmicroplates. As such, these slides 700 can be placed on carrier frameswhich have microplate foot prints so they can be handled within thescreening system 100.

3. Cuvette Rotors

In the diagnostic industry, a wide-range of cuvette systems have beenused including cuvette strips/bars 800 a and rotor cuvette systems 800 b(see FIGS. 8A-8B). For example, the rotor cuvette system 800 b is oftenemployed in combination with a 1-channel liquid handling arrangement andsince it can be mounted directly on a rotary axis it can be very easy toposition with respect to devices for liquid handling or measurement. Thetypical rotor cuvette system 800 b is an injection molded article whichis made from the same plastic materials as those commonly used to makemicroplates. The exemplary rotor cuvette system 800 b shown has 8individual Y-flow through cuvettes 802 where each cuvette 802 cancontain a grating biosensor 804, an optical transducer structure 806, ormicro-optical interferometers 808 (for example). This rotor cuvettesystem 800 b can also be optimized for measurements of absorbence,fluorescence or luminescence, and some of the best known manufacturersof these devices are Hitachi and Olympus. The screening system 100 andthe various principles of measurement described herein can be utilizedto interrogate such cuvette structures 800 a and 800 b.

4. Temperature Distribution in Microplates

A discussion about the temperature distribution of two differentmicroplates 600 which where placed in temperature compensation bodies128 is provided next with reference to FIGS. 9A-9C. The data shown inFIG. 9A was obtained using miniature thermocouplers made of 50 μm thickalumel and chromel wires. These thermocouplers had a low heat capacityand high temperature resolution thus they where very well suited fortemperature measurement tasks in microplate wells. FIG. 9A shows thespeed of thermal equilibration. In contrast, the temperature measurementshown in FIG. 9B was effected with a cresol red dye mixture in a 96-wellmicroplate 600 that was interrogated by a commercially availablemicroplate reader operating at a transmission of 405 nm. While, FIG. 9Cillustrate the readings associated with a 384-well microplate 600containing a temperature-sensitive fluorescence indicator which wasinterrogated by a commercially available microplate fluorescence reader.As can be seen, the temperature compensation bodies 128 helped addressproblematical fluctuations in temperatures within these microplates 600.Other ways that can be used to help compensate for temperaturefluctuations in addition to the equilibration system 106 are discussednext:

4.1 Temperature Compensation Interrogation Scheme with the Adjacent Wellin a Microplate

One method which can also help compensate for temperature fluctuatingduring measurements of binding events in microplates 600 involves thealternating use, with respect to columns or lines, of sample wells andreference (buffer) wells within the microplate 600. This is achieved,for example, by using a 96 pipettor having an indexing mechanism toapply 288 well sample array and 96 well buffer array to a 384-wellmicroplate according to the diagram shown in FIG. 10.

4.2 Temperature Compensation Interrogation Scheme within a Single Wellin a Microplate

Another method which can also help compensate for temperaturefluctuations involves the interrogation of a single well which has botha reference region and a sample region. In this interrogation scheme,each well has a biosensor therein with a diffraction grating structurethat has a blocked region which does not interact with a sample and isthus suitable to be used as a reference area for comparison with therest of the diffraction grating that has the sample located thereon (seeFIG. 11A). The close proximity of the reference region to the sampleregion helps to considerably improve the compensation of the temperatureespecially when compared to the method which uses adjacent wells. Plus,this particular interrogation scheme utilizes less wells when comparedto the method which uses adjacent reference and sample wells to takeinto account temperature fluctuations.

Alternatively, interferometric sensors 1100 which have at least twomeasuring arms 1102 a and 1102 can be used in this particularinterrogation scheme (see FIG. 11B). In this case, a comparabletemperature compensation effect can be obtained, because the signal ofthe interferometer is actually generated, as a matter of principle,during superposition of two optical paths. Thus, if both paths arelocated under the influence of the liquid of one well, then thetemperature difference between the two paths decreases with theincreasing geometrical proximity of the two paths. FIG. 11B illustratesexemplary interferometric sensors 1100 which have two measuring arms1102 a and 1102 b.

5.0 Temperature Compensation Body for RIFS Transducer/Sensor

FIG. 12 is a block diagram illustrating a couple of wells 1202 in amicroplate 1204 (sensor carrier 110) which has a glass bottom plate 1206that is configured as an RIFS transducer 1208 which is in full surfacecontact with a flat temperature compensation body 1210 (e.g. flat metalblock of copper or aluminum). If the microplate 1204 and in particularthe RIFS transducer 1208 is in full contact with the metal block 1210(that is located on the plate carousel 130) for a sufficiently longtime, then the temperature differences between the wells 1202 are goingto be compensated.

6.0 Temperature Compensation Body for Grating Sensors

FIG. 13 shows an exemplary “pitted” thermal bridge 1302 (temperaturecompensation body 1302) which can be used for the temperaturecompensation of the bottom 1304 of a microplate 1306 (sensor carrier110) (which contains grating sensors 612). Alternatively, the entirebottom 1304 of the microplate 1306 may contact the entire surface of aflat metal block. However, if the microplate 1306 has a glass bottom1304 then this alternative may not work well since there is a risk ofdamaging the diffraction grating etc. . . . This risk is even moreprevalent when the microplate 1306 has a plastic bottom 1304 which meansthat if there are “pits” in the region of the diffraction grating/sensorthen this helps ensure greater safety and at the same time helps ensurea sufficiently quick temperature compensation.

7. Temperature Compensation Body for Surface Plasmon Resonance (SPR)Sensors

Compared with the two preceding temperature compensation bodies 1210 and1302 designed to interface with microplates 1204 and 1306 which haveplanar bottoms, there can be specially designed temperature compensationbodies 128 that provide temperature compensation for microplates withmore complex bottoms. For instance, FIG. 14 shows a portion of a SPRmicroplate 1402 (sensor carrier 110) which is placed on top of atemperature compensation body 1404 whose topology is essentially anegative of the topology of the SPR sensor's bottoms 1406.

8. Temperature Compensation Body for Waveguide Interferometer

As was the case which was described above with the grating sensors, itis also possible to adapt a temperature compensation body 1504 to matchthe planar bottom of a microplate 1508 (sensor carrier 110) which haswaveguide interferometers 1506 located therein. In this case, to reducethe risk of local damage, a pit-shaped recess 1502 is provided in thetemperature compensation body 1504 near the region of the coupling-inand coupling-out gratings of the waveguide interferometers 1506. Incontrast, to the simple grating sensor, the temperature compensation iseffected in this case by having direct contact with the sensor region.This is possible because the sites of the recesses 1502, i.e. thecoupling-in and coupling-out regions, have a geometrical distance fromthe sensor 1506.

If desired, the microplate 1508 (and other sensor carriers 110) may havea bottom coated with a substance to help optimize the surface resistancewith a temperature compensation body 1504 (or other temperaturecompensation bodies 128). For instance, the microplate 1508 (and othersensor carriers 110) can have their bottoms coated with a galvaniccoating like the one commonly used to manufacture circuit boards.Although such coatings have only a comparatively low heat capacity, theycan still help ensure a very quick temperature distribution and a verygood thermal contact with a temperature compensation body 128.

9. Measurement Chamber 104/Handling System 112/Equilibration System 106(See FIGS. 1A-1B)

In one embodiment, the exemplary measurement chamber 104 is a thermallyinsulated, temperature-controlled vessel within which a temperature of3° C. above room temperature is usually maintained. The temperaturecontrol can be effected by a circulated air system whose circuit usesPeltier elements as heat exchangers. A controller can also be used toprovide a closed-loop temperature control with the aid of a platinumelectronic temperature sensor integrated into its control circuit.

The measurement chamber 104 can be provided with a simple flapmechanism, through which the sensor carriers 110 can be transported onthe take in/out mechanism 118. The flap mechanism could be held closedby a spring. The transport of the sensor carriers 110 is effected by thetake in/out mechanism 118 which is mounted to a linear guide and moved,for example, by a stepper motor using a toothed belt. The take in/outmechanism 118 moves and pushes the flap open which is considerablysimpler than using complicated baffle mechanisms. The linear guide ofthe take in/out mechanism 118 terminates in the range of action of thevertically movable gripper 113, which is part of the internal platehandling system 112.

The preferred gripper 113 has multiple transfer/holding positions withinthe measurement chamber 104 including: (1) the barcode reading position;(2) the take in/out mechanism 118; (3) the measurement nest 302 on thex-y moveable table 122; and (4) the temperature compensation bodies 128on the different levels of the plate carousel 130. The gripper 113 canreach all of these positions by making one single movement along avertical linear guide which ensures a very quick transfer of thetemperature compensated sensor carriers 110 from the plate carousel 130to the x-y moveable table 122 and this prevents the occurrence ofunnecessary changes in the temperature of the sensor carriers 110. Thebarcode reading position is preferably located at a height between thex-y moveable table 122 and the lowest level of the plate carousel 130:The barcode reader should be mounted at an orientation that is relativeto the sensor carrier 110 while it is secured by the gripper 113.

The plate carousel 130 includes a plurality of equilibration sites 126(on which are secured the temperature compensation bodies 128) which canbe connected by thin, fiber-reinforced plastic rods to a central column132, for example. The central column 132 is provided with a rotationbearing and is moved, for example, by a stepper motor using a toothedbelt. The levels and the allocation of space between the equilibrationsites 126 (including the height of a sensor carrier 110 and thetemperature compensation bodies 128) on one level are selected such thatthe gripper 113 can move between them. Thus, with respect to therotation of the plate carousel 130, there is a plurality of, in thisexample, four positions in which the gripper 113 can be verticallydisplaced. The different positions of the plate carousel 130 and of thegripper 113 are monitored by combinations of position sensors andincremental angle sensors that are associated with the various steppermotors.

If desired, the equilibration sites 126/temperature compensation bodies128 can have: (1) conical positioning elements which function to helpalign the sensor carriers 110; and (2) suitable recesses which providethe free space for the required movement of the gripper 113. The gripper113 itself can be embodied as a form-locking three-finger gripper 113which grips the bottom of the sensor carrier 110. A force-locking gripcould also be used but it is generally considered as not being so safeand as being less convenient for transferring the sensor carriers 110 tothe measurement position.

In the lowermost position, corresponding to the range of movement of thegripper 113, there is the measurement nest 302 of the x-y moveable table122 (which is supported on air bearings) (see FIG. 3). This measurementnest 302 (which can have the form of a temperature compensation body128) is designed such it has recesses to make room for the fingers ofthe gripper 113. In addition, the measurement nest 302 can havespring/ball elements, which align the sensor carrier 110 in a definedmanner relative to the frame. Typically, the gripper 113 usually pushesthe sensor carrier 110 in the direction of the A1 corner of themeasurement nest 302. Then, the gripper 113 applies a verticallydirected force on the sensor carrier 110 to overcome the resilient forceof the spring/ball elements and ensure a defined support of the sensorcarrier 110 in the measurement nest 302.

10. Measurement System 108 for Grating Sensors

As shown in FIG. 16, this particular measurement device 108 has aplurality of serially arranged fiber-optical scanning elements 1602, acommon semi-conductor light source 1604 (with splitter 1606), and oneopto-electronic spectrometer 1608 (with coupler 1610) per measurementchannel. Typically, the sensor carrier 110 is scanned in thelongitudinal (x) direction by moving the x-y moveable table 122. Then,the scanning track is changed at right angles, so that each biosensor612 in each well 610 can be measured along a (y) direction in one ormore places. The scanning operation itself is synchronized by a pathmeasurement system, which is part of the x-y moveable table 122. Thispath measurement system has a sub-μm path resolution. For a moredetailed discussion about an exemplary measurement system 108 referenceis made to U.S. Pat. No. 6,829,073 (the contents of which areincorporated by reference herein).

Each sensor carrier 110 is typically measured at least twice. A firstmeasurement is effected without binding molecules and is referred to asa baseline measurement. The second measurement is effected with thebinding molecule and is referred to as an end-point measurement. For thebaseline measurement, the sensor carrier 110 is charged with a bufferoutside the screening system 100 and is incubated at room temperaturefor a sufficient time. Then, the sensor carrier 110 is placed on thetransport carriage 118 (take in/out mechanism 118) and transported intothe screening system 100. Thereafter, the temperature of the sensorcarrier 110 is determined, the barcode is read, and the sensor carrier110 is placed by the handling system 112 onto a computer-addressedtemperature compensation body 128 in the plate carousel 130 (see FIGS.1A-1F). This operation is repeated until the first of the sensorcarriers 110 has been on the temperature compensation bodies 128 for asufficiently long time. That is, until the temperature equilibration ofthe first sensor carrier 110 is complete such that the gripper 113 candeposit this sensor carrier 110 onto the measurement nest 302 of the x-ymoveable table 122 which is then moved over to the measurement device108. This sensor carrier 110 is scanned to obtain one or more readingsof the so-called baseline measurement, and then it is transported out ofthe measurement chamber 104. This operation is repeated until the lastsensor carrier 110 of this particular series of sensor carriers 110 hasbeen baseline measured.

Once, the sensor carriers 110 have been baseline measured, they arecharged with binding molecules by an external liquid handling unitoutside of the screening system 100 and are incubated for a sufficientlylong time. After this incubation step, the sensor carriers 110 aretransported into the screening system 100 a second time, equilibratedand measured (end-point measurement). By offsetting the two readingsagainst each other, the parameters of the binding behavior of themolecules per well in the sensor carriers 110 can be obtained. Theoverlapping operation of storing the sensor carriers 110 for baselineand end-point measurements on top of the temperature compensation bodiesfor the purpose of equilibration in the screening system 100 can beenabled by suitable software, e.g. a scheduler. To this end, it isimportant that the equilibration times for both steps of themeasurements are not below a predetermined minimum threshold.

11. Temperature Equilibration in Microplates

The temperature development over time in an exemplary microplate 600(sensor carrier 110) without using a temperature compensation body 128(carriage 128) and with using a temperature compensation body 128(carriage 128) is shown in FIGS. 17A-17D (where the ‘0’ time in thegraphs indicates the point when the microplate 110 is first placed ontop of the temperature compensation body 128). If a constant temperatureof approximately 0.2 K is required over the entire microplate 110, thenthese readings show that this value is reached with the aid of thetemperature compensation body 128 after approximately 20 minutes. Thistime is the minimum equilibration time and knowing this time allows oneto determine the required storage capacity of the plate carousel 130. Itis clear that without the use of a temperature compensation body 128then a considerably greater storage capacity would be required on theplate carousel 130. If a greater storage capacity is required then thisalso means that increasingly long paths are needed to transport themicroplates 110, which in turn takes more time and may even change theequilibration-generated temperature profile on the microplates 110.Thus, the equilibration time of the microplates 110 spent on thetemperature compensation bodies 128 directly affects the requiredstorage capacity on the plate carousel 130 and also the sensitivity ofthe measurement analyses.

12. Measurement Device 108 for Waveguide Interferometers

As described above, a sensor carrier 110 with waveguide interferometers612 located therein could also be transferred to a measurement nest 302on the x-y moveable table 122 which can then perform a scanning movementover the measurement device 108. In this case, the measurement device108 would be similar to the Fraunhofer measurement device 108′ shown inFIG. 18. The Fraunhofer measurement device 108′ has several beamsplitters 1802 (one shown) which operate in parallel to couple lightinto each well and in particular into each of the two interferometerarms 1804 a and 1804 b of the waveguide interferometers 612 with thehelp of a coupling-in grating 1806 (see also FIG. 11B). After, the lightpasses through these two sensor regions 1804 a and 1804 b, it is coupledout by a coupling-out grating 1808 (per well) and passed through adouble slit 1810 and imaged in a superimposed manner onto a CCD sensor1812. The interferogram thus generated represents the difference inrefractive index between the two waveguides 1804 a and 1804 b in thewaveguide interferometer 612.

13. Measurement Device 108 for RIFS Transducer/sensor

As described above, a sensor carrier 110 with RIFS transducers/sensors612 located therein could also be transferred to a measurement nest 302on the x-y moveable table 122 which can perform a scanning movement overthe measurement device 108. In this case, the measurement device 108would be similar to the ZEISS measurement device 108″ shown in FIG. 19.This particular measurement device 108″ includes an image-generatingwhite light interferometer 1902 and a monochromater 1904 which directslight through a wedge-shaped end window 1906 that is shown located belowthe RIFS transducer/sensor 612. Then, a CCD sensor 1908 would receivevia a lens 1910 the light reflected from RIFS transducer/sensor 612.

Although multiple embodiments of the present invention have beenillustrated in the accompanying Drawings and described in the foregoingDetailed Description, it should be understood that the invention is notlimited to the embodiments disclosed, but is capable of numerousrearrangements, modifications and substitutions without departing fromthe spirit of the invention as set forth and defined by the followingclaims.

1. A screening system capable of controlling at least one of movementand storage of a sensor carrier therein to ensure there is asubstantially constant temperature gradient present across at least aportion of the sensor carrier, further comprising a temperatureequilibration system which includes a temperature compensation body onwhich the sensor carrier is stored for a predetermined amount of time toensure there is a substantially constant temperature gradient presentacross the at least a portion of the sensor carrier, and a temperaturesensor which measures an incoming temperature of the sensor carrier andthen the measured incoming temperature is used to calculate thepredetermined amount of time that the sensor carrier needs to be placedon said temperature compensation body to ensure there is a substantiallyconstant temperature gradient present across the at least a portion ofthe sensor carrier.
 2. The screening system of claim 1, wherein saidtemperature compensation body has a bottom which is configured to matcha bottom of the sensor carrier and is also configured to not damagesensors within the sensor carrier.
 3. A screening system, comprising: atemperature equilibration system which includes a temperaturecompensation body on which a sensor carrier is stored for apredetermined amount of time to ensure there is a substantially constanttemperature gradient across at least a portion of the sensor carrier; ameasurement system which interrogates one or more sensors located withinthe sensor carrier when there is still the substantially constanttemperature gradient present across at least a portion of the sensorcarrier; and a temperature sensor which measures an incoming temperatureof the sensor carrier and then the measured incoming temperature is usedto calculate the predetermined amount of time that the sensor carrierneeds to be placed on said temperature compensation body to ensure thereis a substantially constant temperature gradient across the at least aportion of the sensor carrier.
 4. The screening system of claim 3,wherein said temperature compensation body has a bottom which isconfigured to match a bottom of the sensor carrier and is alsoconfigured to not damage the sensors within the sensor carrier.
 5. Ascreening system comprising: a measurement chamber; a take in/outmechanism which receives a sensor carrier and moves the sensor carrierto inside said measurement chamber, said measurement chamber contains atleast the following: a handling system; a temperature equilibrationsystem which has a plate holder with one or more layers where each ofthe layers has a plurality of temperature compensation bodies; a tablewhich has a measurement nest; wherein said handling system takes thesensor carrier from said take in/out mechanism and places the sensorcarrier onto one of the temperature compensation bodies to help equalizea temperature of the sensor carrier; and wherein said handling systemafter a period of time takes the sensor carrier from the one temperaturecompensation body of said temperature equilibration system and placesthe sensor carrier into the measurement nest of said table; ameasurement system which interrogates one or more sensors located withinthe sensor carrier when the sensor carrier is located on the measurementnest of the table; and a control unit for controlling said take in/outmechanism, said handling system, said temperature equilibration system,said table and said measurement system to perform a measurement analysison the sensors located within the sensor carrier.
 6. The screeningsystem of claim 5, wherein each temperature compensation body in saidtemperature equilibration system has a bottom which is configured tomatch a bottom of the sensor carrier and is also configured to notdamage the sensors within the sensor carrier.
 7. The screening system ofclaim 5, wherein said handling system moves the sensor carrier in avertical motion to/from said take in/out mechanism, said temperatureequilibration system and said table.
 8. The screening system of claim 5,wherein said sensor carrier is pushed-down or sucked-down onto the onetemperature compensation body.
 9. The screening system of claim 5,wherein said sensor carrier includes: a microplate; a bar; a strip; aslide; or a cuvette.
 10. The screening system of claim 5, wherein saidsensor carrier has a bottom coated with a substance to help ensure arelatively good thermal contact with the temperature compensation body.11. The screening system of claim 5, wherein said sensor includes: aresonant waveguide grating biosensor; a reflectometric interferencespectroscopy sensor; a waveguide interferometer; or a surface plasmonresonance sensor.
 12. The screening system of claim 5, wherein saidcontrol unit can perform the measurement analysis by executing a highthroughput screening protocol to interrogate a plurality of the sensorcarriers by combining baseline and end-point measurements with themovement of the plurality of sensor carriers into and out of themeasurement nest in said moveable table.
 13. The screening system ofclaim 5, wherein said table is a stationary table or a moveable table.14. The screening system of claim 5, wherein said plate holder is aplate carousel.
 15. The screening system of claim 5, further comprisinga temperature sensor which measures a temperature of the sensor carrierwhen said take in/out device brings the sensor carrier into saidmeasurement chamber.
 16. The screening system of claim 15, wherein saidtemperature sensor includes one of the following: an infrared sensor; anelectronic contact thermometer; a combination of a color sensor locatedwithin the measurement chamber and temperature-sensitive dyes located onthe sensor carrier; or a temperature module located on the sensorcarrier which interacts with a radio-frequency based transponder locatedon the sensor carrier which transmits the temperature of the sensorcarrier to said control unit.
 17. The screening system of claim 15,wherein said control unit obtains the temperature of the sensor carrierand determines if a planned storage time of the sensor carrier on top ofthe one temperature compensation body within the temperatureequilibration system is sufficient to obtain a desired temperatureprofile on the sensor carrier.
 18. The screening system of claim 15,wherein said control unit uses the temperature of the sensor carrieralong with a measured internal temperature and a measured internalhumidity within said measurement chamber to calculate whether there is arisk of water condensing on the sensor carrier.